Hepatic expression profiling has revealed miRNA changes in liver diseases, while hepatic miR-155 expression was increased in murine non-alcoholic fatty liver disease, suggesting that miR-155 might regulate the biological process of lipid metabolism. To illustrate the effects of miR-155 gain of function in transgenic mouse liver on lipid metabolism, transgenic mice (i.e., Rm155LG mice) for the conditional overexpression of mouse miR-155 transgene mediated by Cre/lox P system were firstly generated around the world in this study. Rm155LG mice were further crossed to Alb-Cre mice to realize the liver-specific overexpression of miR-155 transgene in Rm155LG/Alb-Cre double transgenic mice which showed the unaltered body weight, liver weight, epididymal fat pad weight and gross morphology and appearance of liver. Furthermore, liver-specific overexpression of miR-155 transgene resulted in significantly reduced levels of serum total cholesterol, triglycerides (TG) and high-density lipoprotein (HDL), as well as remarkably decreased contents of hepatic lipid, TG, HDL and free fatty acid in Rm155LG/Alb-Cre transgenic mice. More importantly, microarray data revealed a general downward trend in the expression profile of hepatic genes with functions typically associated with fatty acid, cholesterol and triglyceride metabolism, which is likely at least partially responsible for serum cholesterol and triglyceride lowering observed in Rm155LG/Alb-Cre mice. In this study, we demonstrated that hepatic overexpression of miR-155 alleviated nonalcoholic fatty liver induced by a high-fat diet. Additionally, carboxylesterase 3/triacylglycerol hydrolase (Ces3/TGH) was identified as a direct miR-155 target gene that is potentially responsible for the partial liver phenotypes observed in Rm155LG/Alb-Cre mice. Taken together, these data from miR-155 gain of function study suggest, for what we believe is the first time, the altered lipid metabolism and provide new insights into the metabolic state of the liver in Rm155LG/Alb-Cre mice.

Single nucleotide polymorphisms (SNPs) in Programmed cell death 1 (PD-1) gene may contribute to the development of cancer. In this study, we selected PD-1 rs10204525 T>C, rs2227982 A>G, rs36084323 T>C and rs7421861 A>G polymorphisms and designed a hospital-based case-control study to determine the potential relationship between these functional SNPs in PD-1 gene and esophagogastric junction adenocarcinoma (EGJA) risk. A total of 1,063 EGJA patients and 1,677 controls were enrolled from Eastern Chinese Han population. SNPscanTMgenotyping assay was used to analyze the genotyping of PD-1 polymorphisms. We found that PD-1 rs7421861 A>G polymorphism was associated with the development of EGJA. However, PD-1 rs2227982 A>G polymorphism was a protective factor for EGJA. In addition, PD-1 rs36084323 CC homozygote genotype might be associated with a borderline decreased risk of EGJA. In a subgroup analysis, a decreased risk of EGJA in never drinking and never smoking groups was identified. Haplotype comparison analysis suggested that PD-1 Trs10204525Grs2227982C36084323Ars7421861 haplotype significantly decreased the risk of EGJA. However, Trs10204525Grs2227982C36084323Grs7421861 haplotype in PD-1 gene may confer risk to EGJA. In conclusion, our study highlights rs2227982 A>G, rs36084323 T>C and rs7421861 A>G polymorphisms and haplotypes in PD-1 gene, especially within the intron region, are significantly associated with the risk of EGJA. Further case-control studies with larger sample size and detailed gene-environmental data to replicate these findings in different populations are needed to validate our conclusion.

To assess the potential effects of Cytotoxic T-lymphocyte antigen 4 (CTLA4) gene polymorphisms on susceptibility to gastric cardia adenocarcinoma (GCA), we genotyped four polymorphisms (rs733618 A>G, rs16840252 C>T, rs231775 G>A and rs3087243 G>A) in CTLA4 and calculated odds ratios (ORs) with the corresponding 95% confidence intervals (95% CIs) for the genotype and allele distributions between GCA cases and controls. The CTLA4 genotypes were determined by the polymerase chain reaction-ligase detection reaction (PCR-LDR) analysis in 330 GCA patients and 608 unrelated cancerfree controls. In this case-control study, there was no significant difference in the genotype and allele distributions of four CTLA4 polymorphisms between GCA patients and controls. However, haplotype association analysis indicated that compared with CTLA4 G rs733618 C rs16840252 G rs231775 C rs3087243 , CTLA4 G rs733618 C rs16840252 A rs231775 G rs3087243 and A rs733618 C rs16840252 G rs231775 A rs3087243 haplotypes conferred increased risks of GCA (OR = 6.46, 95% CI = 1.33-31.28; P = 0.012; both); however, CTLA4 A rs733618 C rs16840252Ars231775 G rs3087243 and A rs733618 T rs16840252 G rs231775 G rs3087243 haplotypes conferred decreased risks of GCA (P = 0.001 and P = 0.011, respectively). These results highlight that the rare CTLA4 haplotypes may affect the development of GCA in the Chinese population.

Background: Recurrent laryngeal nerve (RLN) injury is one of the most frequent postoperative complications of esophageal squamous cell carcinoma (ESCC) radical resection. This study aims to develop a novel scoring system to predict recurrent laryngeal nerve lymph node (RLNLN) metastases in early ESCC and explore the indications for precise RLN lymphadenectomy. Results: A total of 311 cases selected from 1,466 ESCC patients were divided into the dissection group and the control group. Age, tumor length, macroscopic tumor type, T stage, tumor location and tumor differentiation were independent predictors of RLNLN metastases. The weighted scoring system included age (+2 for <56 years), tumor length (+2 for over 4.45 cm), tumor location (+4 for upper thoracic, +2 for mid-thoracic) and macroscopic tumor type (+1 for advanced type). The total number of points estimated the probability of RLNLN metastases [low-risk (0-2 point), 0%; moderate-risk (3-4 points), 9.8%; and highrisk (>4 points), 43.4%]. Besides, the dissection group had more complications and similar survival rate when compared with the control group.Conclusions: We developed a novel scoring system that accurately estimated the risk of RLNLN metastases in early ESCC patients. RLN lymphadenectomy may be safely omitted for the patients in the low-risk subgroup.

Aim To assess the exosomal miR‐21/Let‐7a ratio, a noninvasive method, in distinguishing non‐small cell lung cancer (NSCLC) from benign pulmonary diseases. Methods The exosomes were extracted from the peripheral blood serum using serum exosomal extraction kit. miR‐21 and Let‐7a levels were evaluated by quantitative reverse transcription polymerase chain reaction. Results We found that miR‐21/Let‐7a ratio of NSCLC patients was significantly higher than that of healthy people, patients with pulmonary inflammation diseases, and benign pulmonary nodules, respectively. Receiver‐operating characteristic analysis revealed that as compared with healthy controls, miR‐21/Let‐7a produced the area under the curve (AUC) at 0.8029 in patients with NSCLC, which helped to distinguish NSCLC from healthy controls with 81.33% sensitivity and 69.57% specificity. In addition, the AUC of miR‐21/Let‐7a in NSCLC patients was 0.8196 in comparison to patients with pulmonary inflammation diseases. Meanwhile, the sensitivity and specificity were 56.00% and 100%, respectively. Furthermore, compared with patients with benign pulmonary nodules, the AUC of miR‐21/Let‐7a in NSCLC patients was 0.7539. The sensitivity and specificity were 56.00% and 82.61%, respectively. Conclusion In the present study, our findings revealed that exosomal miR‐21/Let‐7a ratio holds considerable promise as a noninvasive biomarker for the diagnosis of NSCLC from benign pulmonary diseases.